Effects of oxidized LDL versus IL-1ß/TNF-ɑ/INFɣ on human gingival mesenchymal stem cells properties.

IF 3.4 3区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Journal of periodontal research Pub Date : 2024-07-02 DOI:10.1111/jre.13319

Karim Fawzy El-Sayed, Elena Mahlandt, Kristina Schlicht, Kim Enthammer, Johannes Tölle, Juliane Wagner, Katharina Hartmann, Peter R Ebeling, Christian Graetz, Mathias Laudes, Christof E Dörfer, Dominik M Schulte

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Abstract

Aims: Oxidized low-density lipoprotein (oxLDL) is an important player in the course of metabolic inflammatory diseases. oxLDL was identified in the gingival crevicular fluid, denoting possible associations between oxLDL-induced inflammation and periodontal disease. The current investigation compared for the first-time direct effects of oxLDL to a cytokine cocktail of IL-1ß/TNF-ɑ/INF-γ on gingival mesenchymal stem cells' (G-MSCs) attributes.

Methods: Human third passage G-MSCs, isolated from connective tissue biopsies (n = 5) and characterized, were stimulated in three groups over 7 days: control group, cytokine group (IL-1β[1 ng/mL], TNF-α[10 ng/mL], IFN-γ[100 ng/mL]), or oxLDL group (oxLDL [50 μg/mL]). Next Generation Sequencing and KEGG pathway enrichment analysis, stemness gene expression (NANOG/SOX2/OCT4A), cellular proliferation, colony-formation, multilinear potential, and altered intracellular pathways were investigated via histochemistry, next-generation sequencing, and RT-qPCR.

Results: G-MSCs exhibited all mesenchymal stem cells' characteristics. oxLDL group and cytokine group displayed no disparities in their stemness markers (p > .05). Next-generation-sequencing revealed altered expression of the TXNIP gene in response to oxLDL treatment compared with controls (p = .04). Following an initial boosting for up to 5 days by inflammatory stimuli, over 14 day, cellular counts [median count ×10^-5 (Q25/Q75)] were utmost in control - [2.6607 (2.0804/4.5357)], followed by cytokine - [0.0433 (0.0026/1.4215)] and significantly lowered in the oxLDL group [0.0274 (0.0023/0.7290); p = .0047]. Osteogenic differentiation [median relative Ca²⁺ content(Q25/Q75)] was significantly lower in cytokine - [0.0066 (0.0052/0.0105)] compared to oxLDL - [0.0144 (0.0108/0.0216)] (p = .0133), with no differences notable for chondrogenic and adipogenic differentiation (p > .05).

Conclusions: Within the current investigation's limitations, in contrast to cytokine-mediated inflammation, G-MSCs appear to be minimally responsive to oxLDL-mediated metabolic inflammation, with little negative effect on their differentiation attributes and significantly reduced cellular proliferation.

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氧化低密度脂蛋白与 IL-1ß/TNF-ɑ/INFɣ 对人类牙龈间充质干细胞特性的影响

目的：氧化低密度脂蛋白（oxLDL）是代谢性炎症疾病过程中的一个重要角色。在牙龈缝隙液中发现了oxLDL，这表明oxLDL诱导的炎症与牙周疾病之间可能存在关联。目前的研究首次比较了 oxLDL 和 IL-1ß/TNF-ɑ/INF-γ 鸡尾酒细胞因子对牙龈间充质干细胞（G-MSCs）属性的直接影响。方法：从结缔组织活组织切片（n = 5）中分离并鉴定的人类第三通道 G-MSCs 分为三组，刺激 7 天：对照组、细胞因子组（IL-1β[1 ng/mL]、TNF-α[10 ng/mL]、IFN-γ[100 ng/mL]）或 oxLDL 组（oxLDL [50 μg/mL]）。通过组织化学、新一代测序和 RT-qPCR，研究了下一代测序和 KEGG 通路富集分析、干性基因表达（NANOG/SOX2/OCT4A）、细胞增殖、集落形成、多线性潜能和细胞内通路的改变：G-间充质干细胞具有间充质干细胞的所有特征。下一代测序显示，与对照组相比，TXNIP基因的表达对oxLDL处理的反应有所改变（p = .04）。在炎症刺激下，细胞计数[中位数×10-5 (Q25/Q75)]最初增加了最多 5 天，在 14 天内，对照组的细胞计数[中位数×10-5 (Q25/Q75)]最高[2.6607 (2.0804/4.5357)]，其次是细胞因子[0.0433 (0.0026/1.4215)]，而 oxLDL 组的细胞计数显著降低[0.0274 (0.0023/0.7290); p = .0047]。成骨分化[相对 Ca2+ 含量中位数（Q25/Q75）]在细胞因子组[0.0066 (0.0052/0.0105)] 明显低于在 oxLDL 组[0.0144 (0.0108/0.0216)] (p = .0133)，软骨和成脂分化无明显差异（p > .05）：结论：在当前调查的局限性范围内，与细胞因子介导的炎症不同，G-间充质干细胞似乎对氧化亚低密度脂蛋白介导的代谢性炎症反应很小，对其分化属性几乎没有负面影响，但细胞增殖明显减少。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of periodontal research 医学-牙科与口腔外科

CiteScore

6.90

自引率

5.70%

发文量

103

审稿时长

6-12 weeks

期刊介绍： The Journal of Periodontal Research is an international research periodical the purpose of which is to publish original clinical and basic investigations and review articles concerned with every aspect of periodontology and related sciences. Brief communications (1-3 journal pages) are also accepted and a special effort is made to ensure their rapid publication. Reports of scientific meetings in periodontology and related fields are also published. One volume of six issues is published annually.